This project is concerned with the transport and metabolic fate of proteins in the kidney and with the regulation of renin release by the kidney. Its major physiological implication concerns the elucidation of the quantitative aspects of both renal handling of proteins and renin release by the kidney. Additionally, the results may shed light on the phenomena of pathological proteinuria and on the pathophysiology of the renin-angiotensin-aldosterone system. With respect to protein transport by the kidney, little is known about its quantitative aspects, although renal cell uptake of both exogenous and endogenous filtered proteins is now a well established fact. Our results, obtained with lysozyme as a tracer molecule, suggest that a part of the normal filtered load of protein is reabsorbed intact across the renal tubular epithelium. These results led us to hypothesize that reabsorption of intact protein represents an important way by which the kidney handles a normal filtered load of protein, while a catabolic pathway may be utilized in situations of protein overload (e.g. nephrosis, increase in plasma levels of protein, massive injection of foreign proteins). The central aim of this part of the project is to test quantitatively this hypothesis. For this purpose we will use the isolated perfused rat kidney, as the principal experimental preparation. With respect to the regulation of renin release by the kidney, our major aim is to determine the relative sensitivity of the receptors to the several signals which have been postulated to regulate the rate of renin release (e.g. sodium load to the distal tubules, baro-receptors at the afferent arterioles, humoral and hormonal factors, such as catecholamines, angiotensin, aldosterone). Hopefully, this determination will elucidate the physiological significance of these factors.